Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: (1) define the role of hepatitis C viral response to pegylated interferon-based therapy (2) evaluate novel therapeutic strategies in the management of hepatitis C virus (HCV) among HIV co-infected individuals, (3) develop novel genomic and proteomic markers that predict hepatitis C viral response to existing and newer therapies and (4) develop in vitro culture systems using infectious clones of HCV genotypes that will enable us to study immunologic control of HCV and develop novel therapeutics against HCV. Analyses of the kinetics of the viral response to hepatitis C therapy in H CV/HIV co-infected individuals suggest that it may be possible to predict long term response to anti-HCV therapy based on the initial response of the level of HCV in the plasma. Using combination therapy of pegylated interferon together with ribavirin in these subjects, we are determining whether genomic and proteomic markers can predict response to therapy prior to initiation of treatment. Another clinical trial that completed enrollment determined more frequent doses of pegylated interferon in the first 4 weeks of therapy in combination with ribavirin can enhance the viral kinetic response to HCV therapy in persons with HCV and HIV infection. A new clinical trial using albumin-conjugated interferon alpha (Albuferon) to treat hepatitis C among HIV-infected patients will begin enrollment later this year.